First-line osimertinib (Tagrisso, AstraZeneca) demonstrated superiority to older generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in overall survival (OS) benefit for patients with EGFR-mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), according to late-breaking results of the FLAURA trial presented at the ESMO Congress 2019 in Barcelona, Spain.

“The survival results are both statistically significant and clinically meaningful with first-line osimertinib for EGFR-mutated patients,” study author Suresh Ramalingam, MD, FASCO, Winship Cancer Institute of Emory University, said in a statement. “This is the first time a TKI has proven to extend survival relative to another TKI in lung cancer therapy.”

Osimertinib is a third-generation, irreversible, oral EGFR-TKI developed to inhibit both EGFRm+ and EGFR T790M resistance mutations.

The FLAURA trial, which included treatment-naïve patients with Ex19del/L858R EGFRm+ advanced NSCLC, evaluated the efficacy and safety of osimertinib 80 mg orally once daily versus comparator EGFR-TKI (either erlotinib or gefitinib).

Previously-reported study findings showed that the primary endpoint of progression-free survival (PFS) was met. With survival data in the study now mature, the results further reinforce the superiority of osimertinib in this treatment setting, Dr Ramalingam noted.  

According to the data, the median OS with osimertinib was 38.6 months versus 31.8 months with first generation EGFR-TKIs, with a hazard ratio of 0.799 (p=0.0462). The study also showed that 54% of patients treated with osimertinib were alive at 3 years compared with 44% in the standard care group.

According to Dr Ramalingam, these OS results in the control group are among the highest reported in EGFR inhibitor patients.

After disease progression, 31% of patients in the control group switched to the osimertinib arm, representing 47% of patients in the control group who received post-study therapy. This is consistent with the real-world setting, since only approximately 50% of patients develop the T790M mutation, according to the authors.

Because of its high selectivity, osimeritinib also demonstrates a more favorable safety profile than other treatments.

“FLAURA met both its primary and key secondary endpoints and showed a favorable safety profile for osimertinib,” Dr Ramalingam concluded. “The results further reinforce the clinical utility and superiority of osimertinib in the front-line setting. Based on these data, osimertinib should be the preferred front-line therapy for EGFR-mutated lung cancer patients.”

References

1. LBA5_PR: Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis. Annals of Oncology. Presented by: Suresh S. Ramalingam at ESMO Congress 2019. September 27-October 1, 2019. Barcelona, Spain.

2. Front-line osimertinib improves overall survival in EGFR-mutation positive NSCLC [news release]. ESMO Congress 2019. Accessed September 28, 2019.